American Journal of Medical Genetics Supplement 6:42-47 (1990)
Oral Aspects of Rubinstein-Taybi Syndrome Raoul C.M. Hennekam and Jaap M. Van Doorne Clinical Genetics Center (R.C.M.H.) and Department of Maillofacial Prosthodontics, State University of Utrecht (J.M.V.D.), Utrecht, The Netherlands Oral findings in 45 patients with RubinsteinTaybi syndrome living in The Netherlands are compared with those from the literature. The main non-dental findings were thin upper lip, small oral opening, pouting lower lip, retrol micrognathia, and apparently highly arched, narrow palate. Cleft uvula, cleft palate, or, rarely, cleft upper lip can be part of the syndrome. Timing of the eruption of deciduous and permanent dentition is normal. Sixty-two percent of patients have malpositioned, crowded teeth. Marked caries was found in 36% and was possibly caused by problems in dental care due to the small opening of the mouth, malposition and malformation of the teeth, and non-cooperation of the patients. Hypodontia, hyperdontia, and natal teeth can be manifestations of the syndrome. In 73% of all patients and in 92% of all permanent dentitions, talon cusps were found. Two or more talon cusps are rarely found in the normal population or other syndromes. Therefore, this finding strongly supports the diagnosis of Rubinstein-Taybi syndrome in patients in whom this diagnosis is suspected. KEY WORDS: oral anomalies, palato-schisis, talon cusp INTRODUCTION Several parts of the mouth and oral cavity are important clues for clinicians to diagnose the RubinsteinTaybi syndrome (RTS)[Gorlin et al., 1976;Jones, 19881. A small opening of the mouth and an apparently highly arched and narrow palate are especially well-known findings often mentioned in the literature. Much less attention has been paid to dental anomalies. In a review of 293 papers concerning RTS, we found a description of Received for publication June 12, 1989; revision received July 25, 1989. Address reprint requests to R.C.M. Hennekam, M.D., Clinical Genetics Center Utrecht, P.O. Box 18009,3501 CA Utrecht, The Netherlands. This work is dedicated to Bob Gorlin for his continuing invaluable teaching in clinical genetics.
0 1990 Wiley-Liss, Inc.
the teeth in 76 papers (98 cases); 66 papers mentioned abnormalities. Specific attention to dental anomalies in RTS has been paid before in 3 papers [Gardner and Girgis, 1979; Kinirons, 1983; Baker, 19871. Therefore, we performed dental investigations in a group of individuals with RTS living in The Netherlands, and compared the findings with the data from literature. MATERIALS AND METHODS A follow-up study of 45 individuals with RTS was started in 1985 by one of us (R.C.M.H.).A detailed description of the patients is published elsewhere in this issue [Hennekam et al., 1990a,bl. Twenty-four patients were investigated by a dentist (J.M.V.D.). Although in all 24 an OrthoPantomoGram (OPG) was made, the radiographs were of sufficient quality to analyze in only 18patients. In the other 6 patients either the patient did not allow radiography or moved or was malpositioned during radiography, making assessment unreliable. Of the 21 other patients, 7 were edentulous. One patient died in infancy. In the remaining 13 patients, investigation by a dentist was impossible because of anxiety regarding dental investigations, or parental refusal. Their dental status was recorded by an instructed clinical geneticist (R.C.M.H.)during routine physical examination. Special attention was paid to the presence of talon cusps. Lip and lingual mobility were assessed during logopedic investigations, which were performed in 25 patients [Hennekam et al., submitted]. A literature search, documenting 293 references with 407 patients with RTS as primary focus [Hennekam, this issue], was done with special attention for dental and other oral and perioral findings. RESULTS The main perioral and oral non-dental findings are compared with literature figures in Table I and illustrated in Figures 1 and 2. None of the patients had a bifid uvula, palatoschisis, or bifid tip of the tongue. It is noteworthy that after completing the study, one of us (R.C.M.H.) diagnosed a 44-year-old woman who had a cheilognathopalatoschisis. The main dental findings are tabulated in Table I1 and illustrated in Figures 3-5. In all 8 edentulous patients the teeth were extracted in the second or third decade because of extensive caries. One had had a complete double row of upper incisors. Parents reported problems in daily tooth care in 43%,mainly inadequate
Oral Aspects of RTS
43
TABLE I. Perioral and Oral Non-Dental Findings in 45 Dutch Individuals With RTS Compared t o 98 Individuals With RTS in the Literature Findings Thin upper lip Small opening of mouth Pouting lower lip Poor lip mobility Mandibular prognathism Retro4micrognathia Appearing highly arched, narrow palate Bifid uvula Palatoschisis Bifid tip of tongue Marked median groove in tongue Poor lingual mobility Short frenulum
Dutch study, % 47 64 42 24a 28 64 89
o 0 o
7 20 56
Literature 40% 56% 38% n.m.h 26% 56% 93% 5 patientsb 6 patients' 5 patientsd 1 patients' 2 patients' 2 patientsg
Investigated in 25 patients [Hennekam et al., submitted]. bCoffn [19641, Robinson et al. [19661, McDonagh [19681, Salmon [1968], Gravinghoff and Tost [19701. ' McDonagh [1968],Verma [19701,and Rahfling et al. [19711: cleft soft palate; Rassolini et al. (19781, Selmanowitz and Stiller (19811, and Musumeci et al. [19841: cleft palate. Levy-Leblond et al. [1969], Rett et al. [19691, Russell et al. (19711, Sehabiague [19771, Sautarel et al. [19781. Verma [1970l. Filippi [19721, Gotts and Liemohn [19771. JBliu and Saint-Rome (19671, Levy-Leblond et al. [1969l. n.m. not mentioned. a
brushing because of irregularly formed and placed teeth. In 35%there were problems in dental care bv the dentist. In one patient this was caused by a very small oral opening. In all others anxiety gave most problems. The more intensive treatments were generally done during general anaesthesia. The findings from the literature study are tabulated in Tables I and 111, and included short uvula [Filipi, 1972; Lopez Delgado et al., 19811, broad uvula [Rubinstein and Taybi, 19631, large tongue [Jeliu and SaintRome, 1967; Nespoli and Bottelli, 19751, furrowed tongue [Laing and Harper, 19671, deciduous teeth still present at age 22 [Filipi, 19721, natal teeth [Sinnette and Odeku, 19681, irregular incisal edges [Rett et al., 1969; Kerrien, 19741, dens invaginatus [Kinirons, 19831, chronic gingivitis [Wilson et al., 19891, dental abscess [Selmanowitz and Stiller, 19811, maxillary odontoma [Taybi and Rubinstein, 19651, broad alveolar ridges [Rubinstein and Taybi, 1963; Roy et al., 19681, and enamel hypoplasia [Walker and Cox, 1969; De Toni et al., 19821.
DISCUSSION The non-dental findings in the present group of patients correspond well with those found in the literature. In 11literature patients bifid uvula and/or cleft palate was described. In several Dutch patients the palate was so high and slit-like that an undetected submucous cleft could have been present. Additional investigations to prove this could not be performed. The eruption of both the deciduous teeth and permanent teeth is in agreement with normal eruption [Schulze, 1970; Dixon and Stewart, 1976; Kooi, 19821.
Fig. 1. Note short upper lip and pouting lower lip.
The finding of one patient with natal teeth is not unusual. The incidence of natal and neonatal teeth (eruption before the 3rd month) among whites was estimated to be one in 3,000 [Bodenhoff and Gorlin, 1963; Anderson, 19821. The irregular and crowded placement of the teeth is probably caused by the underdevelopment of the jaws, giving less space than normal. In several Dutch patients, teeth were extracted to make sufficient room for the remaining teeth to normalize dental position and to facilitate dental care.
Fig. 2. Note high, slit-like palate (resembling a curved Chinese roof3 [Kinirons, 19831 and malpositioned teeth.
44
Hennekam and Van Doorne TABLE 11. Dental Findings in 37 Dutch RTS Patients
N Deciduous teeth Permanent teeth
26
Total
37
a
11
Eruption first element Mean 9 mo (0-17) Mean 6.4 yr (4.6-8.2)
Eruption last element Mean 3-6 yr (1.9-5.3) Mean 13.3 yr (11.1-15.8)
Irregularly placed,
Increased caries,
Hypodontid hyperodontia,
Talon cusps,
%
%
%
%
75
20
33133
60
41
29112
9 (27). 92
62.5
36
30115
73
Other (No. of patients) 2 natal teeth (1) Small incisors (1) Chronic gingivitis (1) Small incisors and cuspids (2)
In addition 2 patients had evidence of talon cusps of unerupted incisors on their OrthoPanthomoGram.
It remains uncertain whether increased dental caries is solely caused by difficult brushing due to the small oral opening, dental malposition and malformation, and non-cooperation,or whether enamel hypoplasia plays a significant role. We have not had the opportunity as yet to study extracted teeth. The incidence of hypodontia (other than the 3rd molars) among whites is between 2.7 and 6.0%, and the incidence of hyperodontia lies between 0.5 and 3.0% [Dixon and Stewart, 1976; Bodin et al., 1978; Brook, 1984; Buenviaje and Rapp, 19841. In the present study 30%of the patients had hypodontia and 15%hyperodontia. This is considerably higher than the frequencies given in the literature for both. The most important finding in the present study is the very high incidence of talon cusps in the permanent dentition (92%). A talon cusp is an accessory cusplike structure on the lingual side mostly of incisors (Figs. 3-51, The term “talon cusps” was chosen because of the resemblance in shape to an eagle’s talon. Most talon cusps occur on maxillary incisors, but there are a few reports of mandibular incisors [Mellor and Ripa, 1970; Goldstein and Medina, 1974; Mader, 1982; Falomo,
19831and of maxillary canines [Rantanen, 1971;Goel et al., 19761.Talon cusps are more frequently found in the permanent dentition [Henderson, 1977; Mass et al., 1978; Mader and Kellogg, 19851. Some talon cusps contain a pulp horn; others do not [Rantanen, 1971; Natkin et al., 1983; Mader and Kellogg, 19851. Talon cusps can
Fig. 4. Dental model showing high, narrow palate, malpositioned molars, and talon cusp formation on 2 lateral incisors.
Fig. 3. Schematic drawing of a talon cusp (arrow) compared with a normal incisor. The talon cusp may also contain a pulp chamber.
Fig. 5. OrthoPantomoGram showing talon cusp formation on all 4 upper incisors.
Oral Aspects of RTS TABLE 111. Dental Finding in 98 Individuals With RTS in the Literature Finding
Patients
Normal teeth Malpositioned or crowded teeth Increased caries Discolored teeth Hyperodontia Hypodontia Small teeth Large teeth Talon cusps Double row of teeth
23/98 patients 53/98 patients 15/98 patients 4"
3b 3' 2" 9* 2g
a Rubinstein and Taybi [19631, Kerrien [1974l: yellowish; Johnson [1966], Lahlou and Carrier [19711: brownish. Weiland [19691, Lopez Delgado et al. [1981l: double upper medial incisor. Baker [19871: double 2nd mandibular premolar. 'JBliu and Saint-Rome [1967], Bejar and Smith (19691, Roldan [1969l. Rubinstein and Taybi [ 19631, Herrmann and Opitz 119691, Scanabissi and Neri [1970l, Soto Viera and Garcia Castro [19711, Marin et al. [1972], Renda [19721, DAttoma [19781, De Toni et al. [19821. McArthur [1967], Prosperi and Ricotti Chessa [19751. Sakurai et al. [19661, Gardner and Girgw I19791, Kinirons [19831, Baker [19871. g h h l f i n g et al. [19711, Lopez Delgado et a1 [1981l.
be seen during normal inspection of the dentition, or on radiographs. Normally crowns of incisors are sufficiently calcified to be seen on radiographs around age one year, making talon cusps in the non-erupted permanent incisors radiographically visible a t that time. After the first description of Mitchell in 1892,50patients with talon cusps were described in literature [Davis and Brook, 19861; 1 5 other patients have been described since then. Nine had RTS [Sakurai et al., 1966; Gardner and Girgis, 1979; Kinirons, 1983; Baker, 19871. In the Pittsburgh study of 2,439 children, 4 cases with talon cusps were found, giving a n incidence of 0.17% [Buenviaje and Rapp, 19841. These authors did not state the ethnic background of their population, nor whether it occurred in the deciduous or permanent dentition, nor whether the patients had one or more teeth involved. The incidence among people of Chinese descent was reported to be higher than in other ethnic groups [Chen and Chen, 1986; Davis and Brook, 19861. Chawla et al. [1983] found a n incidence of 7.7% among North Indian children, using a much wider criterion for making the diagnosis of talon cusps. All individuals with RTS with talon cusps from literature had at least 2 [Baker, 19871,but mostly had 4, teeth involved [Sakurai et al., 1966; Gardner and Girgis, 1979; Kinirons, 19831. Ten normal individuals from other studies were reported with 2 talon cusps [Dayal et al., 1980; Davis and Brook, 19861 and 3 patients with 4 or more talon cusps [Rantanen, 1971; Goldstein and Medina, 1974; Goel et al., 19763. The mean number of talon cusps in the present study was 3.9, with all patients having at least 2 teeth involved (in one patient 8 teeth were affected). Talon cusps have been reported once in Mohr syndrome [Goldstein and Medina, 19741, in Sturge-Weber dysplasia [Chen and Chen, 19861, and in Williams syndrome [Kwee and Lindhout, 19891. Talon cusps may
45
cause complications, mainly increased caries, irritation of the tongue during speech and mastication, accidental cusp fracture, advanced attrition causing pulpal exposure or periapical pathoses, and misinterpretations of radiographs prior to eruption [Chen and Chen, 19861. Although in some patients treatment is not necessary, others require a reduction or even removal of (part of) the cusp [Myers, 1980; Pitts and Hall, 1983; Shey and Eytel, 19831. The origin of talon cusps remains obscure. Some authors favor enlargement of a n enamel tubercle, lingual to the cingulum [Shafer et al., 19831, others enlargement of the cingulum itself [Gardner and Girgis, 19791. The finding of hyperodontia associated with talon cusps [Goldstein and Medina, 1974; Myers, 1980; Mader, 1981; Davis and Brook, 1986; present study1 points to the possibility of a fusion with a supernumerary element, or incomplete duplication. The complete double rows of incisors described in literature [Rohlfing et al., 1971; Ldpez Delgado et al., 19811 and in one of the present patients support this suggestion. There are 2 reports of familial occurrence of talon cusps [Goldstein and Medina, 1974; Davis and Brook, 19861. In conclusion, thorough inspection of the oral cavity with special attention to the dentition could give additional support for the diagnosis of RTS. If on 2 or more incisors talon cusps are seen in a patient that is suspected to have RTS the diagnosis is very probable. In children with deciduous dentition and doubts about the diagnosis, radiographs of the maxillary incisors may be helpful, although making such radiographs in children with mental retardation is often difficult.
ACKNOWLEDGMENTS This study was made possible partly by gifts of the Nationale Collecte voor Geestelijk Gehandicapten and the Nederlands Comite voor Kinderpostzegels. We thank Dr. R.J. Gorlin (Minnesota, U S A . ) for critical review of the manuscript. REFERENCES Anderson RA (1982): Natal and neonatal teeth: Histologic investigation of two black females. J Dent Child 49:300-303. Baker MA (1987):Dental and oral manifestations of Rubinstein-Taybi syndrome: Report of case. J Dent Child 54:369-371. Bejar RL, Smith GF (1969):Broad thumbs and great toes syndrome. J Fla Med Assoc 56:lll-114. Bodenhoff J, Gorlin FLJ (1963): Natal and neonatal teeth. Pediatrics 32:1087-1093. Bodin I, Julin P, Thomsson M (1978): Hyperodontia. Dentomaxillofac Radio1 7:E-17. Brook AH (1984):A unifying aetiological explanation for anomalies of human tooth number and size. Arch Oral Biol 29:373-378. Buenviaje TM, Rapp R (1984):Dental anomalies in children: A clinical and radiographic survey. J Dent Child 51:42-46. Chawla HS, Tewari H, Gopalakrishnan NS (1983): Talon c u s p A prevalence study. J Indian SOCPedod Prev Dent 1:28-34. Chen RJ,Chen HS (1986): Talon cusp in primary dentition. Oral Surg Oral Med Oral Pathol 62:67-72. Coffin GS (1964): Brachydactyly, peculiar facies and mental retardation. Am J Dis Child 108:351-359. DAttoma G (1978): Sindrome di Rubinstein-Taybi. Agg Pediatr 29:47-50.
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Davis PJ, Brook AH (1986):The presentation of talon cusp: Diagnosis, clinical features, associations and possible aetiology. Br Dent J 160:84-88. Dayal PK, Mani J N , Verma PK (1980): Talon cusp: A review and case report. J Dent 8:85-87. De Toni T, Cavaliere G, Cortese M, Gastaldi R, Carozzino L, Duillo MT (1982): La sindrome di Rubinstein-Taybi. Presentazione di due nuovi casi. Minerva Pediatr 34:765-770. Dixon GH, Stewart RE (1976): Genetic aspects of anomalous tooth development. In Stewart RE, Prescott GH (eds): “Oral Facial Genetics.” St. Louis: C.V. Mosby Company, pp 124-150. Falomo 00 (1983): Talon cusp. A case report. Odontostomatol Trop 4:207, 208. Filippi G (1972): The Rubinstein-Taybi syndrome. Report of 7 cases. Clin Genet 3:303-318. Gardner DG, Girgis SS (1979): Talon cusps: A dental anomaly in the Rubinstein-Taybi syndrome. Oral Surg Oral Med Oral Pathol 47:519-521. Goel VP, Rohatgi VK, Kaushik K (1976):Talon cusp-A clinical study. J Indian Dent Assoc 48:425-427. Goldstein E, Medina J L (1974):Mohr syndrome or oral-facial-digital 11: Report of two cases. J Am Dent Assoc 89:377-382. Gorlin RJ, Pindborg J J , Cohen MM (1976): Rubinstein-Taybi syndrome. In Gorlin RJ, Pindborg JJ, Cohen MM (eds): “Syndromes of the Head and Neck,” Second edition. New York: McGraw Hill Inc., pp 657-660. Gotts EE, Liemohn WP (1977): Behavioral characteristics of three children with the broad thumb-hallux (Rubinstein-Taybi) syndrome. Biol Psychiatry 12:413-423. Gravinghoff J, Tost M (1970): Das Rubinstein-Taybi-Syndrom.Ein Beitrag zum Problem der Determinationsperiode. Monatsschr Kinderheilkd 118:479-484. Henderson HZ (1977): Talon cusp: A primary or a permanent incisor anomaly. J Indiana Dent Assoc 56:45, 46. Hennekam RCM (1990): Bibliography on Rubinstein-Taybi syndrome. Am J Med Genet (this issue). Hennekam RCM, Stevens CA, Van De Kamp J J P (1990a):Recurrence risk in Rubinstein-Taybi Syndrome. Am J Med Genet (this issue). Hennekam RCM, Van Den Boogaard MJ, Sibbles BJ, Van Spijker HG (1990b): Rubinstein-Taybi syndrome in The Netherlands. Am J Med Genet (this issue). Hennekam RCM, Baselier JCA, Beijaert E, Bos A, Blok JB, Jansma JBM, Thorbecke-Nilsen VV. Veerman H: Psychological and speech studies in Rubinstein-Taybi syndrome (submitted). Herrmann J , Opitz J M (1969):Dermatoglyphic studies in a RubinsteinTaybi patient, her unaffected dizygous twin sister and other relatives. In Bergsma D (ed): “The Clinical Delineation of Birth Defects.” Baltimore: For the National Foundation-March of Dimes BD:OAS V (2):22-24. Jeliu G, Saint-Rome G (1967): Le syndrome de Rubinstein-Taybi. A propos d’une observation. Union Med Can 96:22-29. Johnson CF (1966): Broad thumbs and broad great toes with facial abnormalities and mental retardation. J Pediatr 68:942-951. Jones KL (1988):“Smith’s Recognizable Patterns of Human Malformation,” 4th Ed. Philadelphia: W.B. Saunders Co. Kerrien J (1974):Le syndrome de Rubinstein et Taybi. Apropos de deux observations. Thesis (Brest), France. Kinirons MJ (1983): Oral aspects of Rubinstein-Taybi syndrome. Br Dent J 154:46, 47. Kooi SK (1982): Aspecten van het tijdeljk gebit. Thesis (Utrecht), The Netherlands. Kwee ML, Lindhout D (1989): personal communication. Lahlou B, Carrier C (1971): Menom6trorragies et bifidite uterine dans un cas de syndrome du ‘pouse en spatule’ (Rubinstein et Taybi).Rev Int Pediatr 14:5-14. Laintr CR. HarDer WH (1967): Rubinstein-Tavbi svndrome. Broad tKumbs and toes, facial abnormalities and mental ;etardation. Ariz Med 24536-540. Levy-Leblond E, d’oelsnitz M, Vaillant JM, Maroteaux P (1969): Le syndrome de Rubinstein et Taybi (apropos de quatre observations). Arch Fr Pediatr 26523-535.
L6pez Delgado J, Estefania Gallardo C, Santano M, Blanco Yun A, Suarez M (1981): Sindrome de Rubinstein y Taybi. A proposito de cuatro casos. Rev Esp Pediatr 37:157-162. Mader CL (1981): Talon cusp. J Am Dent Assoc 103:244-246. Mader CL (1982): Mandibular talon cusp. J Am Dent Assoc 105651-653. Mader CL, Kellogg SL (1985): Primary talon cusp. J Dent Child 52:223-226. Marin R, Diarnent J , Badanian de Garcia-FoniesR (1972):Sindrome de Rubinstein y Taybi. A proposito de un caso. Arch Pediatr Urug 43:84-93. Mass E, Kaffe I, Buchner A (1978): Talon cusp in deciduous dentition. Isr J Dent Med 27:37, 38. McArthur RG (1967): Rubinstein-Taybi syndrome: Broad thumbs and great toes, facial abnormalities and mental retardation: A presentation of three cases. Can Med Assoc J 96462-466. McDonagh BJ (1968): Syndrome of Rubinstein and Taybi. J Irish Med ASSOC61:273-276. Mellor JK, Ripa LW (1970):Talon cusp: A clinically significant anomaly. Oral Surg Oral Med Oral Pathol 29:225-228. Mitchell WH (1892): Case report. Dent Cosmos 34:1036 (only). Musumeci SA, Colognola RM, Ferri R, Gigli GL, Bergonzi P (1984):Un caso di sindrome di Rubinstein-Taybi (con epilessia e consanguineita dei genitori). Boll Lega Ital Epil 45/46:153-155. Myers C1 (1980): Treatment of a talon cusp incisor: Report of case. J Dent Child 47:119-121. Natkin E, Pitts DL, Worthington P (1983):A case of talon cusps associated with other odontogenic abnormalities. J Endodontol 9491-495. Nespoli L, Bottelli A (1975): Sindrome di Rubinstein-Taybi e sua delimitazione diagnostica. Minerva Pediatr 27:1724-1727. Pitts DL, Hall SH (1983): Talon cusp management: Orthodonticendodontic considerations. J Dent Child 50:364-368. Prosperi P, Ricotti Chessa G (1975):Sindrome di Rubinstein-Taybi con malformazione renale. Minerva Pediatr 27:2230-2238. Rantanen AV (1971): Talon cusp. Oral Surg Oral Med Oral Pathol 32:398-400. Renda Y (1972): Rubinstein-Taybi syndrome. Turk J Pediatr 14:118-124. Rett A, Kahlich-Koenner DM, Mad1 W (1969): Klinische und anthroWien pologische Untersuchungen zum Rubinstein-Taybi-Syndrom. Med Wochenschr 19/20:378-383. Robinson GC, Miller JR, Cook EG, Tischler B (1966):Broad thumbs and toes and mental retardation. Am J Dis Child 111:287-290. Rohlfing B, Lewis K, Singleton EB (1971):Rubinstein-Taybi syndrome. Report of a n unusual case. Am J Dis Child 121:71-74. Roldan EC (1969): Rubinstein-Taybi syndrome. J Maine Med Assoc 60:81-89. Rossolini V, Burroni M, Perrotta F (1978):A proposito di altri due casi di sindrome di Rubinstein-Taybi. Neuropsichiatr Infant 201:445-450. Roy FH, Summitt RL, Hiatt RL, Hughes J G (1968):Ocular manifestations of the Rubinstein-Taybi syndrome. Case report and review of the literature. Arch Ophthalmol 79:272-278. Rubinstein JH, Taybi H (1963): Broad thumbs and toes and facial abnormalities. A possible mental retardation syndrome. Am J Dis Child 105588-608. Russell NA, Hoffman HJ, Bain HW (1971):Intraspinal neurilemoma in association with the Rubinstein-Taybi syndrome. Pediatrics 47:444-447. Sakurai EH, Mitchell DF, Holmes LA (1966):Some craniofacial dysostoses: (Pierre) Robin’s syndrome, Treacher Collins syndrome, and a digito-facial-mental retardation syndrome. Report of three cases. J Oral Med 21:44-47. Salmon MA (1968): The Rubinstein-Taybi syndrome: A report of two cases. Arch Dis Child 43:102-106. Sautarel M, Choussat A, Sandler B, Bui-Authier F, Guiter F, Sehabiague J , Abadie D (1978): Syndrome de Rubinstein-Taybi associe a une triadede Fallot A proposd‘uneobservation. Revuedes complications cardiaques de la maladie. Pediatrie 33593-598.
Oral Aspects of RTS Scanabissi E, Neri G (1970): Osservazioni su un caso di sindrome di Rubinstein-Taybi. Clin Pediatr (Bologna) 52:495-504. Schulze C (1970):Developmental abnormalities of the teeth and jaws. In Gorlin R J , Goldman HM (eds):“Thoma’s Oral Pathology,”6th ed. St. Louis: C.V. Mosby Comp., pp 96, 97. Sehabiague J (1977): A propos d u n e observation associant un syndrome de Rubinstein et Taybi a une triade de Fallot. Thesis (Bordeaux) 202, France. Selmanowitz VJ, Stiller MJ (1981): Rubinstein-Taybi syndrome. Cutaneous manifestations and colossal keloids. Arch Dermatol 117:504-506. Shafer WG, Hine MK, Levy BM (1983):“A Textbook of Oral Pathology,” 4th ed. Philadelphia: W.B. Saunders Comp., pp 40, 41. Shey 2,Eytel R (1983):Clinical management of an unusual case ofdens evaginatus in a maxillary central incisor. J Am Dent Assoc 106:346-348. Sinnette C, Odeku EL (1968): Rubinstein-Taybi syndrome. The first case in an African child and the first case recognized at birth. Clin Pediatr 7:488-492.
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Sot0 Viera ME, Garcia Castro JM (1971): El sindrome de 10s pulgares
anchos (Sindrome de Rubinstein y Taybi): A proposito de un caso. Bol Asoc Med PR 63:59-64. Taybi H, Rubinstein J H (1965): Broad thumbs and toes, and unusual facial features: A probable mental retardation syndrome. Am J Roentgen01 93:362-366. Verma IC (1970): Rubinstein-Taybi syndrome. Case report. Indian J Pediatr 7:672-674. Walker AC, Cox DW (1969): The Rubinstein-Taybi syndrome. Med J Aust 2:99-101. Weiland R (1969): Das Rubinstein-Taybi Syndrom-breiter Daumen und breite Grosszehe mit kranio-mani dbulo-fazialen Missbildungen und geistiger Retardation. Arch Kinderheilkd 179:78-90. Wilson GN, Balir BM, Bilir NA (1989):Intracranial angioblastic meningioma and a n aged appearance in an adult female with Rubinstein-Taybi syndrome. Roc Greenwood Genet Center 8:136 (only).
Oral Aspects of Rubinstein-Taybi Syndrome Raoul C.M. Hennekam and Jaap M. Van Doorne Clinical Genetics Center (R.C.M.H.) and Department of Maillofacial Prosthodontics, State University of Utrecht (J.M.V.D.), Utrecht, The Netherlands Oral findings in 45 patients with RubinsteinTaybi syndrome living in The Netherlands are compared with those from the literature. The main non-dental findings were thin upper lip, small oral opening, pouting lower lip, retrol micrognathia, and apparently highly arched, narrow palate. Cleft uvula, cleft palate, or, rarely, cleft upper lip can be part of the syndrome. Timing of the eruption of deciduous and permanent dentition is normal. Sixty-two percent of patients have malpositioned, crowded teeth. Marked caries was found in 36% and was possibly caused by problems in dental care due to the small opening of the mouth, malposition and malformation of the teeth, and non-cooperation of the patients. Hypodontia, hyperdontia, and natal teeth can be manifestations of the syndrome. In 73% of all patients and in 92% of all permanent dentitions, talon cusps were found. Two or more talon cusps are rarely found in the normal population or other syndromes. Therefore, this finding strongly supports the diagnosis of Rubinstein-Taybi syndrome in patients in whom this diagnosis is suspected. KEY WORDS: oral anomalies, palato-schisis, talon cusp INTRODUCTION Several parts of the mouth and oral cavity are important clues for clinicians to diagnose the RubinsteinTaybi syndrome (RTS)[Gorlin et al., 1976;Jones, 19881. A small opening of the mouth and an apparently highly arched and narrow palate are especially well-known findings often mentioned in the literature. Much less attention has been paid to dental anomalies. In a review of 293 papers concerning RTS, we found a description of Received for publication June 12, 1989; revision received July 25, 1989. Address reprint requests to R.C.M. Hennekam, M.D., Clinical Genetics Center Utrecht, P.O. Box 18009,3501 CA Utrecht, The Netherlands. This work is dedicated to Bob Gorlin for his continuing invaluable teaching in clinical genetics.
0 1990 Wiley-Liss, Inc.
the teeth in 76 papers (98 cases); 66 papers mentioned abnormalities. Specific attention to dental anomalies in RTS has been paid before in 3 papers [Gardner and Girgis, 1979; Kinirons, 1983; Baker, 19871. Therefore, we performed dental investigations in a group of individuals with RTS living in The Netherlands, and compared the findings with the data from literature. MATERIALS AND METHODS A follow-up study of 45 individuals with RTS was started in 1985 by one of us (R.C.M.H.).A detailed description of the patients is published elsewhere in this issue [Hennekam et al., 1990a,bl. Twenty-four patients were investigated by a dentist (J.M.V.D.). Although in all 24 an OrthoPantomoGram (OPG) was made, the radiographs were of sufficient quality to analyze in only 18patients. In the other 6 patients either the patient did not allow radiography or moved or was malpositioned during radiography, making assessment unreliable. Of the 21 other patients, 7 were edentulous. One patient died in infancy. In the remaining 13 patients, investigation by a dentist was impossible because of anxiety regarding dental investigations, or parental refusal. Their dental status was recorded by an instructed clinical geneticist (R.C.M.H.)during routine physical examination. Special attention was paid to the presence of talon cusps. Lip and lingual mobility were assessed during logopedic investigations, which were performed in 25 patients [Hennekam et al., submitted]. A literature search, documenting 293 references with 407 patients with RTS as primary focus [Hennekam, this issue], was done with special attention for dental and other oral and perioral findings. RESULTS The main perioral and oral non-dental findings are compared with literature figures in Table I and illustrated in Figures 1 and 2. None of the patients had a bifid uvula, palatoschisis, or bifid tip of the tongue. It is noteworthy that after completing the study, one of us (R.C.M.H.) diagnosed a 44-year-old woman who had a cheilognathopalatoschisis. The main dental findings are tabulated in Table I1 and illustrated in Figures 3-5. In all 8 edentulous patients the teeth were extracted in the second or third decade because of extensive caries. One had had a complete double row of upper incisors. Parents reported problems in daily tooth care in 43%,mainly inadequate
Oral Aspects of RTS
43
TABLE I. Perioral and Oral Non-Dental Findings in 45 Dutch Individuals With RTS Compared t o 98 Individuals With RTS in the Literature Findings Thin upper lip Small opening of mouth Pouting lower lip Poor lip mobility Mandibular prognathism Retro4micrognathia Appearing highly arched, narrow palate Bifid uvula Palatoschisis Bifid tip of tongue Marked median groove in tongue Poor lingual mobility Short frenulum
Dutch study, % 47 64 42 24a 28 64 89
o 0 o
7 20 56
Literature 40% 56% 38% n.m.h 26% 56% 93% 5 patientsb 6 patients' 5 patientsd 1 patients' 2 patients' 2 patientsg
Investigated in 25 patients [Hennekam et al., submitted]. bCoffn [19641, Robinson et al. [19661, McDonagh [19681, Salmon [1968], Gravinghoff and Tost [19701. ' McDonagh [1968],Verma [19701,and Rahfling et al. [19711: cleft soft palate; Rassolini et al. (19781, Selmanowitz and Stiller (19811, and Musumeci et al. [19841: cleft palate. Levy-Leblond et al. [1969], Rett et al. [19691, Russell et al. (19711, Sehabiague [19771, Sautarel et al. [19781. Verma [1970l. Filippi [19721, Gotts and Liemohn [19771. JBliu and Saint-Rome (19671, Levy-Leblond et al. [1969l. n.m. not mentioned. a
brushing because of irregularly formed and placed teeth. In 35%there were problems in dental care bv the dentist. In one patient this was caused by a very small oral opening. In all others anxiety gave most problems. The more intensive treatments were generally done during general anaesthesia. The findings from the literature study are tabulated in Tables I and 111, and included short uvula [Filipi, 1972; Lopez Delgado et al., 19811, broad uvula [Rubinstein and Taybi, 19631, large tongue [Jeliu and SaintRome, 1967; Nespoli and Bottelli, 19751, furrowed tongue [Laing and Harper, 19671, deciduous teeth still present at age 22 [Filipi, 19721, natal teeth [Sinnette and Odeku, 19681, irregular incisal edges [Rett et al., 1969; Kerrien, 19741, dens invaginatus [Kinirons, 19831, chronic gingivitis [Wilson et al., 19891, dental abscess [Selmanowitz and Stiller, 19811, maxillary odontoma [Taybi and Rubinstein, 19651, broad alveolar ridges [Rubinstein and Taybi, 1963; Roy et al., 19681, and enamel hypoplasia [Walker and Cox, 1969; De Toni et al., 19821.
DISCUSSION The non-dental findings in the present group of patients correspond well with those found in the literature. In 11literature patients bifid uvula and/or cleft palate was described. In several Dutch patients the palate was so high and slit-like that an undetected submucous cleft could have been present. Additional investigations to prove this could not be performed. The eruption of both the deciduous teeth and permanent teeth is in agreement with normal eruption [Schulze, 1970; Dixon and Stewart, 1976; Kooi, 19821.
Fig. 1. Note short upper lip and pouting lower lip.
The finding of one patient with natal teeth is not unusual. The incidence of natal and neonatal teeth (eruption before the 3rd month) among whites was estimated to be one in 3,000 [Bodenhoff and Gorlin, 1963; Anderson, 19821. The irregular and crowded placement of the teeth is probably caused by the underdevelopment of the jaws, giving less space than normal. In several Dutch patients, teeth were extracted to make sufficient room for the remaining teeth to normalize dental position and to facilitate dental care.
Fig. 2. Note high, slit-like palate (resembling a curved Chinese roof3 [Kinirons, 19831 and malpositioned teeth.
44
Hennekam and Van Doorne TABLE 11. Dental Findings in 37 Dutch RTS Patients
N Deciduous teeth Permanent teeth
26
Total
37
a
11
Eruption first element Mean 9 mo (0-17) Mean 6.4 yr (4.6-8.2)
Eruption last element Mean 3-6 yr (1.9-5.3) Mean 13.3 yr (11.1-15.8)
Irregularly placed,
Increased caries,
Hypodontid hyperodontia,
Talon cusps,
%
%
%
%
75
20
33133
60
41
29112
9 (27). 92
62.5
36
30115
73
Other (No. of patients) 2 natal teeth (1) Small incisors (1) Chronic gingivitis (1) Small incisors and cuspids (2)
In addition 2 patients had evidence of talon cusps of unerupted incisors on their OrthoPanthomoGram.
It remains uncertain whether increased dental caries is solely caused by difficult brushing due to the small oral opening, dental malposition and malformation, and non-cooperation,or whether enamel hypoplasia plays a significant role. We have not had the opportunity as yet to study extracted teeth. The incidence of hypodontia (other than the 3rd molars) among whites is between 2.7 and 6.0%, and the incidence of hyperodontia lies between 0.5 and 3.0% [Dixon and Stewart, 1976; Bodin et al., 1978; Brook, 1984; Buenviaje and Rapp, 19841. In the present study 30%of the patients had hypodontia and 15%hyperodontia. This is considerably higher than the frequencies given in the literature for both. The most important finding in the present study is the very high incidence of talon cusps in the permanent dentition (92%). A talon cusp is an accessory cusplike structure on the lingual side mostly of incisors (Figs. 3-51, The term “talon cusps” was chosen because of the resemblance in shape to an eagle’s talon. Most talon cusps occur on maxillary incisors, but there are a few reports of mandibular incisors [Mellor and Ripa, 1970; Goldstein and Medina, 1974; Mader, 1982; Falomo,
19831and of maxillary canines [Rantanen, 1971;Goel et al., 19761.Talon cusps are more frequently found in the permanent dentition [Henderson, 1977; Mass et al., 1978; Mader and Kellogg, 19851. Some talon cusps contain a pulp horn; others do not [Rantanen, 1971; Natkin et al., 1983; Mader and Kellogg, 19851. Talon cusps can
Fig. 4. Dental model showing high, narrow palate, malpositioned molars, and talon cusp formation on 2 lateral incisors.
Fig. 3. Schematic drawing of a talon cusp (arrow) compared with a normal incisor. The talon cusp may also contain a pulp chamber.
Fig. 5. OrthoPantomoGram showing talon cusp formation on all 4 upper incisors.
Oral Aspects of RTS TABLE 111. Dental Finding in 98 Individuals With RTS in the Literature Finding
Patients
Normal teeth Malpositioned or crowded teeth Increased caries Discolored teeth Hyperodontia Hypodontia Small teeth Large teeth Talon cusps Double row of teeth
23/98 patients 53/98 patients 15/98 patients 4"
3b 3' 2" 9* 2g
a Rubinstein and Taybi [19631, Kerrien [1974l: yellowish; Johnson [1966], Lahlou and Carrier [19711: brownish. Weiland [19691, Lopez Delgado et al. [1981l: double upper medial incisor. Baker [19871: double 2nd mandibular premolar. 'JBliu and Saint-Rome [1967], Bejar and Smith (19691, Roldan [1969l. Rubinstein and Taybi [ 19631, Herrmann and Opitz 119691, Scanabissi and Neri [1970l, Soto Viera and Garcia Castro [19711, Marin et al. [1972], Renda [19721, DAttoma [19781, De Toni et al. [19821. McArthur [1967], Prosperi and Ricotti Chessa [19751. Sakurai et al. [19661, Gardner and Girgw I19791, Kinirons [19831, Baker [19871. g h h l f i n g et al. [19711, Lopez Delgado et a1 [1981l.
be seen during normal inspection of the dentition, or on radiographs. Normally crowns of incisors are sufficiently calcified to be seen on radiographs around age one year, making talon cusps in the non-erupted permanent incisors radiographically visible a t that time. After the first description of Mitchell in 1892,50patients with talon cusps were described in literature [Davis and Brook, 19861; 1 5 other patients have been described since then. Nine had RTS [Sakurai et al., 1966; Gardner and Girgis, 1979; Kinirons, 1983; Baker, 19871. In the Pittsburgh study of 2,439 children, 4 cases with talon cusps were found, giving a n incidence of 0.17% [Buenviaje and Rapp, 19841. These authors did not state the ethnic background of their population, nor whether it occurred in the deciduous or permanent dentition, nor whether the patients had one or more teeth involved. The incidence among people of Chinese descent was reported to be higher than in other ethnic groups [Chen and Chen, 1986; Davis and Brook, 19861. Chawla et al. [1983] found a n incidence of 7.7% among North Indian children, using a much wider criterion for making the diagnosis of talon cusps. All individuals with RTS with talon cusps from literature had at least 2 [Baker, 19871,but mostly had 4, teeth involved [Sakurai et al., 1966; Gardner and Girgis, 1979; Kinirons, 19831. Ten normal individuals from other studies were reported with 2 talon cusps [Dayal et al., 1980; Davis and Brook, 19861 and 3 patients with 4 or more talon cusps [Rantanen, 1971; Goldstein and Medina, 1974; Goel et al., 19763. The mean number of talon cusps in the present study was 3.9, with all patients having at least 2 teeth involved (in one patient 8 teeth were affected). Talon cusps have been reported once in Mohr syndrome [Goldstein and Medina, 19741, in Sturge-Weber dysplasia [Chen and Chen, 19861, and in Williams syndrome [Kwee and Lindhout, 19891. Talon cusps may
45
cause complications, mainly increased caries, irritation of the tongue during speech and mastication, accidental cusp fracture, advanced attrition causing pulpal exposure or periapical pathoses, and misinterpretations of radiographs prior to eruption [Chen and Chen, 19861. Although in some patients treatment is not necessary, others require a reduction or even removal of (part of) the cusp [Myers, 1980; Pitts and Hall, 1983; Shey and Eytel, 19831. The origin of talon cusps remains obscure. Some authors favor enlargement of a n enamel tubercle, lingual to the cingulum [Shafer et al., 19831, others enlargement of the cingulum itself [Gardner and Girgis, 19791. The finding of hyperodontia associated with talon cusps [Goldstein and Medina, 1974; Myers, 1980; Mader, 1981; Davis and Brook, 1986; present study1 points to the possibility of a fusion with a supernumerary element, or incomplete duplication. The complete double rows of incisors described in literature [Rohlfing et al., 1971; Ldpez Delgado et al., 19811 and in one of the present patients support this suggestion. There are 2 reports of familial occurrence of talon cusps [Goldstein and Medina, 1974; Davis and Brook, 19861. In conclusion, thorough inspection of the oral cavity with special attention to the dentition could give additional support for the diagnosis of RTS. If on 2 or more incisors talon cusps are seen in a patient that is suspected to have RTS the diagnosis is very probable. In children with deciduous dentition and doubts about the diagnosis, radiographs of the maxillary incisors may be helpful, although making such radiographs in children with mental retardation is often difficult.
ACKNOWLEDGMENTS This study was made possible partly by gifts of the Nationale Collecte voor Geestelijk Gehandicapten and the Nederlands Comite voor Kinderpostzegels. We thank Dr. R.J. Gorlin (Minnesota, U S A . ) for critical review of the manuscript. REFERENCES Anderson RA (1982): Natal and neonatal teeth: Histologic investigation of two black females. J Dent Child 49:300-303. Baker MA (1987):Dental and oral manifestations of Rubinstein-Taybi syndrome: Report of case. J Dent Child 54:369-371. Bejar RL, Smith GF (1969):Broad thumbs and great toes syndrome. J Fla Med Assoc 56:lll-114. Bodenhoff J, Gorlin FLJ (1963): Natal and neonatal teeth. Pediatrics 32:1087-1093. Bodin I, Julin P, Thomsson M (1978): Hyperodontia. Dentomaxillofac Radio1 7:E-17. Brook AH (1984):A unifying aetiological explanation for anomalies of human tooth number and size. Arch Oral Biol 29:373-378. Buenviaje TM, Rapp R (1984):Dental anomalies in children: A clinical and radiographic survey. J Dent Child 51:42-46. Chawla HS, Tewari H, Gopalakrishnan NS (1983): Talon c u s p A prevalence study. J Indian SOCPedod Prev Dent 1:28-34. Chen RJ,Chen HS (1986): Talon cusp in primary dentition. Oral Surg Oral Med Oral Pathol 62:67-72. Coffin GS (1964): Brachydactyly, peculiar facies and mental retardation. Am J Dis Child 108:351-359. DAttoma G (1978): Sindrome di Rubinstein-Taybi. Agg Pediatr 29:47-50.
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anchos (Sindrome de Rubinstein y Taybi): A proposito de un caso. Bol Asoc Med PR 63:59-64. Taybi H, Rubinstein J H (1965): Broad thumbs and toes, and unusual facial features: A probable mental retardation syndrome. Am J Roentgen01 93:362-366. Verma IC (1970): Rubinstein-Taybi syndrome. Case report. Indian J Pediatr 7:672-674. Walker AC, Cox DW (1969): The Rubinstein-Taybi syndrome. Med J Aust 2:99-101. Weiland R (1969): Das Rubinstein-Taybi Syndrom-breiter Daumen und breite Grosszehe mit kranio-mani dbulo-fazialen Missbildungen und geistiger Retardation. Arch Kinderheilkd 179:78-90. Wilson GN, Balir BM, Bilir NA (1989):Intracranial angioblastic meningioma and a n aged appearance in an adult female with Rubinstein-Taybi syndrome. Roc Greenwood Genet Center 8:136 (only).
